The objectives are to study steroid biosynthetic pathways in relation to cancer, using modern chemical-biochemical techniques and approaches. The mechanism of the enzymatic conversion of cholesterol, and its hydroxylation products to the C21 steroids, as it relates to the intermediate steps involved, will be investigated in adrenals and other endocrine tissues from normal and tumor-bearing animals. The animals to be studied will comprise various genetic strains of guinea pigs with and without viral leukemia L2C, carcinogen-induced tumor bearing guinea pigs, rats and mice of various strains, and patients with cancer. Studies will also be done with isolated normal and cancer cell preparations. The enzymatic studies will involve novel kinetic approaches in which the rates of enzyme-substrate interaction vs enzyme-substrate complex reaction to a given product will be determined. Studies are also planned on the biological significance of the hydroxylated cholesterol derivatives at C-20 and C-22. This will be done by studying their occurrence and metabolism in the normal state and in pathological conditions, especially in cancer. The methodology to be used will entail chromatography, isotopes (tritium, deuterium, carbon-14 and oxygen-18) and spectroscopy (ultra-violet, infrared and mass). BIBLIOGRAPHIC REFERENCES: Decomposition of 11-deoxycorticosterone and corticosterone in soda-lime glass. Burstein, S., Steroids 27, 493 (1976). Bile acid synthesis in man: II. Determination of 7 alpha-hydroxycholesterol, (22R)-22-hydroxycholesterol, and 26-hydroxycholesterol in human meconium. Lavi, U., Burstein, S., Gut, M. and Javitt, N.B. J. Lipid Res. (1977), in press.